In vitiligo, regulatory T cells suppress autoimmune responses that worsen disease, but only if they contain the chemokine receptor CCR6, according to a recent study.
- Effector T cells destroy melanocytes, leading to vitiligo lesions.
- Regulatory T cells suppress effector T cell activity and improve disease.
- The chemokine CCR6 is necessary to bring regulatory T cells to the skin, and could be a target for future treatment strategies.
In vitiligo patients, autoreactive CD8+ effector T cells, normally responsible for clearing infections and destroying pathogens, instead, destroy otherwise healthy melanocytes. Regulatory T cells (Tregs) are suppressors of the immune response. In autoimmune diseases, Tregs can block reactive CD8+ T cells from attacking a person’s own cells. Certain Tregs can also exhibit decreased suppressive capability and reduced expression of suppressive genes.
Investigating the Role of Regulatory T Cells in Vitiligo
A recent study published in the Journal of Investigative Dermatology investigated the role of Tregs in vitiligo pathogenesis. In a vitiligo mouse model, mice experimentally depleted of Tregs had less pigmentation than those with intact Tregs. Tregs are recruited to lesioned skin, where they make direct contact with their T effector cell targets, but they require certain chemokine receptors to promote their migration to affected areas.
Role of CCR6 in Treg Migration to the Skin
The chemokine receptor CCR6 was identified as a susceptibility gene for vitiligo. Using T-cell-deficient mice, researchers were able to isolate the role of Tregs with and without CCR6. Mice with no Tregs had extensive depigmentation. Mice with Tregs, but no CCR6, showed no improvement over Treg-deficient mice, whereas mice with CCR6+ Tregs recovered almost all pigmentation, indicating that CCR6 was necessary to improve pigmentation by assisting Treg migration to the skin.
Importance of Understanding the Treg Migration Pathway in Vitiligo
Previous research on the presence and normal functioning of cutaneous Tregs in patients, with the goal of determining if they are present in sufficient numbers, has produced conflicting outcomes. Bringing Tregs to the skin is shown to reduce vitiligo lesion severity by preventing damage by effector T cells. CCR6 is a necessary component of Treg migration and vitiligo suppression. Understanding the Treg migration pathway and how it becomes disrupted in vitiligo will help in the development of better treatment methods.
Source:
Essien, K. I., Katz, E. L., Strassner, J. P., & Harris, J. E. (2022). Regulatory T Cells Require CCR6 for Skin Migration and Local Suppression of Vitiligo. J Invest Dermatol, 142(12), 3158-3166.e3157. https://doi.org/10.1016/j.jid.2022.05.1090
